Abstract

The mechanism by which a number of weak organic acids and bases pass into milk after i.v. infusion was studied. Healthy lactating dairy cows were injected via the jugular vein with appropriate loading doses followed by continuous i.v. infusion for a 6-hr period. Blood and milk samples were taken simultaneously at hourly intervals, milk pH values were deetermined and drug concentrations were measured. Protein binding was determined in milk and plasma using equilibrium dialysis techniques. Theoretical milk-to-plasma ratios for passive diffusive were calculated on the basis of pH partition concepts. Average experimental milk-to-plasma ultrafiltrate ratios of 0.52, 0.27, 0.28 and 1.0 were obtained for salieylic acid (pKa 3.0), p-aminophippurie acid (pKa 3.8), benzoic acid (pKa 4.0) and phenol (pKa 9.9), respectively, with close agreement with theoretical ratios for passive diffusion. The weak organic bases, urea (pKa 0.2), abtipyrine (pKa 1.4), creatinine (pKa 3.4) and ephedrine (pKa 9.6) gave average milk-to-plasma ultrafiltrate ratios of 1.0, 1.0, 1.0 and 4.75 which were in agreement with theoretical ratios for passive diffusion. The experimental milk-to-plasma ultrafiltrate ratios were not affected by changes in drug concentration; however, changes in milk pH values did drastically affect the amount of salicyclic acid, p-aminophippuric acid, benzoic acid and ephedrine that was cleared into the milk. The appearance of these compounds in milk can be satisfactorily explained by diffusion concepts.